Synthesis, characterization, DFT study, DNA/BSA-binding affinity, and cytotoxicity of some dinuclear and trinuclear gold(III) complexes

  • Snežana Radisavljević
  • Dušan Ćoćić
  • Snežana Jovanović
  • Biljana Šmit
  • Marijana Petković
  • Nevena Milivojević
  • Nevena Planojević
  • Snežana Marković
  • Biljana PetrovićEmail author
Original Paper


In this study, we have synthesized a series of dinuclear and trinuclear gold(III) complexes of the general formula [Au2(NN)Cl6] (13) for dinuclear and [Au3(NN)2Cl8]+ (46) for trinuclear compounds, respectively, in which NN is a bidentate ligand (1,4-diaminobutane; 1,6-diaminohexane or 1,8-diaminooctane). These complexes were characterized by elemental analysis, molar conductivity, and spectroscopic techniques (IR, UV–Vis, 1H NMR, ESI–MS). We performed DFT calculations to get insight into the geometry of the studies complexes. DNA-binding studies were performed by UV–Vis spectrophotometry and fluorescence spectroscopy. The results of competitive reactions between gold(III) complexes and ethidium bromide (EB) towards DNA have shown that selected complexes can displace EB from DNA-EB adduct. In addition, these experiments confirm that polynuclear gold(III) complexes interact with DNA covalently or via intercalation. Furthermore, high values of binding constants of gold(III) complexes towards bovine serum albumin (BSA) protein indicate good binding affinity. In addition, redox stability of complexes in the presence of DNA/BSA was confirmed by cyclic voltammetry. Results of the interactions between gold(III) complexes with DNA/BSA were discussed in reference to molecular docking data obtain by Molegro virtual docker. The cytotoxic activity of synthesized gold(III) complexes was evaluated on human breast cancer cell line (MDA-MB-231), human colorectal cancer cell line (HCT-116), and normal human lung fibroblast cell line (MRC-5). All complexes dose-dependently reduced cancer and normal cells viabilities, with significant cytotoxic effects (IC50 < 25 μM) for trinuclear gold(III) complexes (4, 5) on HCT-116 cells.

Graphic abstract


Polynuclear gold(III) complexes DFT Cytotoxicity DNA BSA Molecular docking 



1,4-Diaminobutane; 1,6-diaminohexane or 1,8-diaminooctane)


Calf thymus DNA


Bovine serum albumine


Human breast cancer cell line


Human colon cancer cell line


Normal human lung fibroblast cell line


Phosphate-buffered saline


Dulbecco’s Modified Eagle Medium


Dimethyl sulfoxide


3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


Trimethylsilylpropanoic acid


Ethidium bromide


Statistical software package for Windows, ver. 17, 2008


Inhibitory dose which inhibit 50% growth cells


Highest occupied molecular orbitals


Lowest unoccupied molecular orbitals


Density functional theory


Intrinsic binding constants


Stern–Volmer quenching constant


Quenching rate constant


Number of binding sites per albumin


Viscosity of DNA in the presence of complex


Viscosity of DNA alone


Becke, three-parameter, Lee–Yang–Parr functional


Correlation-consistent polarized valence-only Triple-Zeta basis set


Los Alamos effective core potential triple-zeta basis set


Zero-point vibrational energies


Conductor-like polarizable continuum model


Molegro Virtual Docker version 2013.6.0.1


Crystal structure of DNA in Protein Data Bank


Protein Data Bank


Crystal structure of BSA in Protein Data Bank



The authors gratefully acknowledge financial support of the Ministry of Education, Science and Technological Development of the Republic of Serbia (Project Nos. 172011 and III41010)

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest to declare.

Supplementary material

775_2019_1716_MOESM1_ESM.pdf (1.1 mb)
Supplementary material 1 (PDF 1165 kb)


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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  • Snežana Radisavljević
    • 1
  • Dušan Ćoćić
    • 1
  • Snežana Jovanović
    • 1
  • Biljana Šmit
    • 1
  • Marijana Petković
    • 2
  • Nevena Milivojević
    • 3
  • Nevena Planojević
    • 3
  • Snežana Marković
    • 3
  • Biljana Petrović
    • 1
    Email author
  1. 1.Department of Chemistry, Faculty of ScienceUniversity of KragujevacKragujevacSerbia
  2. 2.“Vinča” Institute of Nuclear ScienceUniversity of BelgradeBelgradeSerbia
  3. 3.Department of Biology, Faculty of ScienceUniversity of KragujevacKragujevacSerbia

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